Alarming increases in prescription drug abuse, especially of opioids, have led to grave concern among stakeholders working to protect the public's health. National surveys and other data sources indicate an escalating epidemic of abuse and a clear connection between opioid use, abuse, poisonings and deaths. Furthermore, for each case of abuse, there are many more cases of non-medical use that raise public health concerns. These changes have prompted investigations to characterize the incidence of abuse as well as risk factors that increase patients' misuse of these therapies. In addition, policy-makers have worked to implement programs that may be effective in reducing non-medical use while not obstructing clinically appropriate treatment of pain. One important type of legislation that states are increasingly pursuing, known as a pill mill law, attempts to restrict the clinica operations of health care clinics that account for disproportionately high volumes of opioid and other controlled substance prescribing. The state of Florida implemented significant legislation in 2011 that systematically regulates many of the root sources of prescription drugs that are diverted, and other states, including Louisiana, Texas and Georgia, have enacted similar legislation. Florida's law is of particular interest as Florida was once recognized as the epicente of prescription drug abuse and diversion in the U.S., and its pill mill law is one of the countrys earliest and most comprehensive. We propose a series of interrelated aims leveraging uniquely granular data to rigorously evaluate the effect of these laws. Our investigation capitalizes upon a database of approximately 5.2 billion longitudinal prescription claims for more than 50 million Americans and 1.5 million prescribers from 2006 through 2013. These data are particularly well suited for the current analyses, since they: capture prescriptions for all sources of payment including cash payment; include a prescriber and pharmacy identifier and also capture prescribing by licensed non-physicians such as dentists and nurse practitioners; extend longitudinally over an eight year period; reflect more than 65% of all prescriptions dispensed in the states of interest; and allow for granular geographic analyses and can be combined with other data to examine policy effects. In addition to examining the aggregate impact of the laws of interest, we will also characterize their effect on subsets of patients, prescribers and pharmacies whose baseline measures suggest unusual patterns of utilization, prescribing or dispensing. Our analyses will be rigorously conducted using advanced epidemiologic and statistical techniques. They will contribute analytic approaches to the pharmacosurveillance of prescription opioids and will yield important information regarding the effect of state laws and regulations for pain clinics on the epidemiology of prescription drug abuse.